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Immunity. 2013 Jan 24;38(1):66-78. doi: 10.1016/j.immuni.2012.09.013. Epub 2012 Nov 21.

Suppressors of cytokine signaling 2 and 3 diametrically control macrophage polarization.

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  • 1Centre for Infection and Immunity, School of Medicine Dentistry and Biomedical Sciences, Queen's University, 97 Lisburn Road, Belfast BT9 7BL, UK.

Erratum in

  • Immunity. 2013 Jul 25;39(1):196-7.

Retraction in

  • Immunity. 2014 Jun 19;40(6):1002.

Abstract

Suppressors of cytokine signaling (SOCS) are important regulators of lipopolysaccharide (LPS) and cytokine responses but their role in macrophage polarization is unknown. We have shown here that myeloid-restricted Socs3 deletion (Socs3(Lyz2cre)) resulted in resistance to LPS-induced endotoxic shock, whereas Socs2(-/-) mice were highly susceptible. We observed striking bias toward M2-like macrophages in Socs3(Lyz2cre) mice, whereas the M1-like population was enriched in Socs2(-/-) mice. Adoptive transfer experiments showed that responses to endotoxic shock and polymicrobial sepsis were transferable and macrophage dependent. Critically, this dichotomous response was associated with enhanced regulatory T (Treg) cell recruitment by Socs3(Lyz2cre) cells, whereas Treg cell recruitment was absent in the presence of Socs2(-/-) macrophages. In addition, altered polarization coincided with enhanced interferon-gamma (IFN-γ)-induced signal transducer and activator of transcription-1 (STAT1) activation in Socs2(-/-) macrophages and enhanced interleukin-4 (IL-4) plus IL-13-induced STAT6 phosphorylation in Socs3(Lyz2cre) macrophages. SOCS, therefore, are essential controllers of macrophage polarization, regulating inflammatory responses.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMID:
23177319
[PubMed - indexed for MEDLINE]
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